Obesity is an increasingly prevalent, costly, and important health problem worldwide. In Western societies such as the United States, the incidence of obesity is approximately 32 percent of the adult population, and the prevalence in children has risen by approximately 40 percent in the last 16 years. It is also rising rapidly in developing countries such as India and China as Western diets and lifestyle are adopted. Although the causes of obesity are multifactorial, these recent increases have been too sudden to be explained by genetic factors.
Population studies conducted in the last decade suggest that environmental factors active during embryonic and fetal development are of substantial consequence for the risk of developing metabolic and cardiovascular disorders in adulthood. The biological basis underlying this concept of "fetal programming" remains speculative but may involve permanent alterations in gene expression that may in turn modify tissue differentiation and hormonal and metabolic regulation.
Some members of the scientific community believe that the fetus adapts to adverse environmental cues while in the womb with permanent readjustments in homeostatic systems to aid survival. However, if these adaptations are inconsistent with the environment encountered after birth, these adaptations may lead to an increased risk of disease. Obesity is one disease associated with impaired fetal development, as children of low birth weight have been shown to develop this disorder in their adult life. However, many reports relating the fetal environment to metabolic disease and adult obesity are confounded as lifestyle influences obscure the linkage between metabolic predisposition and maturity-onset obesity.
Past research has shown that a maternal malnutrition throughout pregnancy in the rat model results in obesity, hypertension, and excessive insulin in the blood in the murine offspring when they reach adulthood. Obesity was not present until after puberty and was associated with overeating. While a high calorie postnatal diet amplified these effects, they also occurred even with a standard postnatal diet. The authors of a new study had noted that the onset of the abnormal eating behaviors occurred before puberty, thus preceding the development of obesity. This observation led to a hypothesis that prenatal maternal environment might also affect other components of behavior associated with an individual's metabolic behavior.
A New Study
A new animal study from New Zealand investigated the effect of the prenatal environment on programming of voluntary locomotor behavior in postnatal life. The authors of "Sedentary Behavior During Postnatal Life is Determined by the Prenatal Environment and Exacerbated by Postnatal Hypercaloric Nutrition" are M. H. Vickers, B. H. Breier, D. McCarthy, and P. D. Gluckman, all from the Liggins Institute, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Their findings are published in the July 2003 edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. The journal is one of 14 scientific journals published each month by the American Physiological Society (APS) (www.the-aps.org).
Virgin Wistar rats (age three months) were mated and included in an animal model of fetal programming using maternal undernutrition. Animals were assigned to one of two nutritional groups, with 15 per group: (1) undernutrition of a standard diet throughout gestation (undernourished group) or (2) a complete standard diet throughout gestation (ad libitum-fed group). Food intake and maternal weights were recorded daily until birth. After birth, pups were weighed, and litter size was recorded. Pups from undernourished mothers were crossfostered onto dams that received ad libitum feeding throughout pregnancy. Litter size was adjusted to eight pups/litter to ensure adequate and standardized nutrition until weaning.
After weaning, male offspring from ad libitum-fed and undernourished mothers were divided into two balanced postnatal groups to be fed either a standard diet or a hypercaloric diet The mineral and vitamin content in the two diets was identical and in accordance with the requirements for standard rat diets.
Two separate studies were undertaken. In the first study, voluntary locomotor activity was assessed in the offspring (six per group of each gender) near puberty and in adulthood (145 days). During trials of 15 minutes duration, animals were examined on distance traveled, stereotypic movement, ambulatory time, time spent resting, and bursts of stereotypic movement. Food intake was also measured over a five-day period from day 140 to day 145. In a second study an identical manipulation was used prenatally, but all rats (eight per group of each gender) were maintained on a normal diet after weaning, and their behavior was studied at 14 months of age.
In the first study, offspring that were undernourished in the womb were significantly more sedentary in postnatal life than those born of mothers with a standard diet for all parameters measured, and independent of postnatal diet. Analysis of ingestive behavior revealed overeating in mature offspring that had been exposed to maternal undernutrition. This was independent of postnatal diet, although sedentary behavior was exacerbated by hypercaloric nutrition.
Importantly, in the animals tested at a peripubertal age, diminished locomotor activity was already present before the development of maturity-onset obesity and was significantly reduced in males compared with females.
In the second trial, offspring of undernourished mothers at 14 months of age were shown to be significantly less active than offspring of normally fed mothers. A gender difference occurred, with males significantly less active than females, but the prenatal effect was significant in each gender. This second study confirms that the sedentary effect is persistent through life, is solely related to prenatal maternal diet, and occurs in both genders.
The prenatal environment can lead to the development of both abnormal eating and exercise behaviors, adding to previous research findings that the environment in the womb can influence physiological features of the metabolic syndrome. This research raises the intriguing possibility that some behaviors and lifestyle choices that exacerbate the metabolic syndrome in humans are an inherent part of the syndrome and may have a prenatal origin. The implications of this hypothesis are profound. If sedentary behavior and overeating are determined during prenatal development, this may explain why public health attempts to improve exercise and to reduce food intake in adults with hypertension, insulin resistance, and hyperlipidemia are often ineffective.
Before this groundbreaking research, evidence that the fetal or early neonatal environment may lead to obesity and inactivity was inconclusive because lifestyle influences obscured the linkage between metabolic predisposition and maturity-onset obesity. This research is the first to clearly separate prenatal from postnatal effects and affirms that lifestyle choices themselves may have a perinatal origin.
The findings reveal that predispositions to obesity, altered eating behavior, and sedentary activity are linked and occur independently of eating habits after birth. Moreover, the prenatal influence seems permanent as offspring of undernourished mothers were still significantly more inactive and obese compared with normal offspring at an advanced adult age, even in the presence of a healthy diet throughout postnatal life.
This research has major implications for public health policy; health care funding may be better spent on improving pregnancy care rather than waiting until metabolic and cardiovascular disorders manifest in adults years or decades later.
Source: July 2003 edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.